Disorders of the Nervous System
Author: Nathaly Azucena Bernal Aguirre | Email: nbernal@fmed.uba.ar
Nathaly A. Bernal Aguirre1°, Juan S. Calanni2°, Ruth E. Rosenstein2°, Damian Dorfman1°
1° Laboratory of retinal neurochemistry and experimental ophthalmology, Department of Human Biochemistry, School of medicine/CEFYBO
2° Department of Biological Chemistry, School of Natural and Exact Sciences/IQUIBICEN, UBA/CONICET, Buenos Aires, Argentina
In previous work we have developed an experimental model of primary optic neuritis (NEO) in rats through the microinjection of lipopolysaccharide (LPS) directly into the optic nerve (ON). Metformin has protective effects in several inflammatory diseases of the central nervous system. We studied the effect of metformin on the retinal and ON alterations induced by experimental NEO. Adult male Wistar rats were injected with 1 μl of LPS (4.5 μg/μl) in one NO and vehicle in the contralateral ON. A group of animals was treated with metformin or vehicle at 24 h before and at 2, 4 and 6 days after the injection of LPS (preventive treatment), or at days 4 and 6 post-LPS/vehicle (delayed treatment). LPS induced a significant and persistent decrease in visual evoked potentials (VEPs) amplitude and light pupillary reflex (RPC), an increase in Iba-1 and glial fibrillary acidic protein (GFAP) immunoreactivity, ON demyelination and loss of ON axons and a significant loss of retinal ganglion cell loss. Moreover, LPS induced an early increase in blood-brain barrier permeability, inflammatory and oxidative stress, as well as a decrease in AMP activated kinase (AMPK) activation at the ON. Pre-treatment with metformin significantly prevented all these alterations, and delayed treatment with metformin significantly reversed the decrease in VEPs and RPC amplitudes caused by LPS. These results suggest that metformin could be considered a new (potentially translatable) strategy to treat human NEO.